The aortic and arterial vulnerability spectrum: A conceptual biological framework for risk stratification and precision surgical decision-making in aortopathy and arteriopathy

OBJECTIVE: To introduce the Aortic and Arterial Vulnerability Spectrum (AAVS), a biologically grounded conceptual framework designed to improve risk stratification and surgical decision-making in aortopathy and arteriopathy by incorporating substrate-level insights. METHODS: The framework was developed using a structured, hypothesis-driven process that integrates high-reliability systems theory, extracellular matrix biology, and clinical outcome patterns. A novel application of skin biopsy is introduced as a tissue-level surrogate for aortic wall integrity. Histological and transmission electron microscopy analyses were used to identify gradable ultrastructural features of collagen and elastin organization. The AAVS framework defines three biological risk domains, substrate vulnerability, clinical fragility, and mechanisms of failure, each linked to a proposed scoring system under development. Clinical case illustrations demonstrate conceptual utility. RESULTS: The three domains of biological risk are (1) substrate vulnerability, assessed through the AAVS Score of histological; and ultrastructural analysis of skin biopsy as a surrogate for aortic tissue integrity; (2) clinical fragility, captured by the Vascular Fragility Score, which quantifies phenotypic indicators of vascular fragility from clinical history, physical findings, and imaging; and (3) mechanisms of failure, modeled by substrate vulnerability progression, a longitudinal, dynamic modeling system that tracks substrate vulnerability progression over time toward aortic failure and includes vascular health modifiers that alter mismatch progression over time. CONCLUSIONS: AAVS introduces a structured clinical reasoning framework and skin biopsy-based scoring approach for risk stratification in aortopathy and arteriopathy. It reframes failure as a progressive biological process shaped by substrate integrity, not just anatomy or procedural success. Although the scoring systems remain under development, the cognitive framework offers immediate utility for case interpretation, biologically matched surgical planning, and future longitudinal modeling. Ongoing work aims to validate the scoring systems and refine biological risk assessment across diverse clinical cohorts.